{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:18:46Z","timestamp":1787026726214,"version":"build-2736575974"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T00:00:00Z","timestamp":1628553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1A5A2015385"],"award-info":[{"award-number":["2017R1A5A2015385"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19AI142735"],"award-info":[{"award-number":["U19AI142735"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003627","name":"Rural Development Administration","doi-asserted-by":"publisher","award":["PJ0156400"],"award-info":[{"award-number":["PJ0156400"]}],"id":[{"id":"10.13039\/501100003627","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    Nontuberculous mycobacterial pulmonary infection is often aggravated due to antibiotic resistance issues. There is a need for development of new drugs inducing both host immune responses and antimicrobial activities. This study shows that the rufomycins 4\/5\/6\/7 (Rufomycin 4\u20137), which targets ClpC1 as a subunit of caseinolytic protein complex ClpC1\/ClpP1\/ClpP2 of mycobacteria, exhibits a dual effect in host innate defense and\n                    <jats:italic>in vivo<\/jats:italic>\n                    antimicrobial activities against a rough morphotype of\n                    <jats:italic>Mycobacterium abscessus<\/jats:italic>\n                    (Mabs-R), a clinically severe morphotype that causes hyperinflammation. Rufomycin 4\u20137 treatment showed antimicrobial effects against Mabs pulmonary infection\n                    <jats:italic>in vivo<\/jats:italic>\n                    and in macrophages. In addition, Rufomycin 4\u20137 significantly decreased inflammation, but enhanced the autophagy\/lysosomal genes through upregulation of the nuclear translocation of transcription factor EB (TFEB). Furthermore, Rufomycin 4\u20137 treatment effectively inhibited mitochondrial damage and oxidative stresses in macrophages during Mabs-R infection. Collectively, Rufomycin 4\u20137-mediated dual effects inducing both antimicrobial activities and host immune defense might confer an advantage to treatment against Mabs-R infection.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2021.695024","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T03:29:55Z","timestamp":1628566195000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Rufomycin Exhibits Dual Effects Against Mycobacterium abscessus Infection by Inducing Host Defense and Antimicrobial Activities"],"prefix":"10.3389","volume":"12","author":[{"given":"Cho Rong","family":"Park","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seungwha","family":"Paik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Jae","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Kyung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Min","family":"Jeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Hee","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jake","family":"Whang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhua","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo-Won","family":"Suh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gauri","family":"Shetye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Nong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"McAlpine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido F.","family":"Pauli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Franzblau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanghyun","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Kyeong","family":"Jo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,10]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"E943","DOI":"10.1073\/pnas.1321390111","article-title":"Mycobacterium abscessus cording prevents phagocytosis and promotes abscess formation.","volume":"111","author":"Bernut","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e1005986","DOI":"10.1371\/journal.ppat.1005986","article-title":"Mycobacterium abscessus-induced granuloma formation is strictly dependent on TNF signaling and neutrophil trafficking.","volume":"12","author":"Bernut","year":"2016","journal-title":"PLoS Pathog."},{"key":"B3","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1084\/jem.20102049","article-title":"Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS).","volume":"208","author":"Bulua","year":"2011","journal-title":"J. Exp. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e0117657","DOI":"10.1371\/journal.pone.0117657","article-title":"Mycobacterium abscessus morphotype comparison in a murine model.","volume":"10","author":"Caverly","year":"2015","journal-title":"PLoS One"},{"key":"B5","doi-asserted-by":"crossref","first-page":"e2204","DOI":"10.1128\/AAC.02204-18","article-title":"Rufomycin Targets ClpC1 Proteolysis in Mycobacterium tuberculosis and M. abscessus.","volume":"63","author":"Choules","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"B6","doi-asserted-by":"publisher","first-page":"5868","DOI":"10.3390\/ijms20235868","article-title":"Mycobacterium abscessus, an emerging and worrisome pathogen among cystic fibrosis patients.","volume":"20","author":"Degiacomi","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.3389\/fmicb.2018.01613","article-title":"Challenges of NTM drug development.","volume":"9","author":"Falkinham","year":"2018","journal-title":"Front. Microbiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1099\/mic.0.28625-0","article-title":"Spontaneous reversion of Mycobacterium abscessus from a smooth to a rough morphotype is associated with reduced expression of glycopeptidolipid and reacquisition of an invasive phenotype.","volume":"152","author":"Howard","year":"2006","journal-title":"Microbiology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1111\/j.1462-5822.2007.00914.x","article-title":"Intracellular signalling cascades regulating innate immune responses to Mycobacteria: branching out from Toll-like receptors.","volume":"9","author":"Jo","year":"2007","journal-title":"Cell. Microbiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1111\/j.1600-0463.2012.02932.x","article-title":"Phagocytosis and cytokine response to rough and smooth colony variants of Mycobacterium abscessus by human peripheral blood mononuclear cells.","volume":"121","author":"Jonsson","year":"2013","journal-title":"APMIS"},{"key":"B11","doi-asserted-by":"publisher","first-page":"125","DOI":"10.3389\/fimmu.2019.00125","article-title":"Phagosome escape of rough Mycobacterium abscessus strains in murine macrophage via phagosomal rupture can lead to type I interferon production and their cell-to-cell spread.","volume":"10","author":"Kim","year":"2019","journal-title":"Front. Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e1008294","DOI":"10.1371\/journal.ppat.1008294","article-title":"Mycobacterium abscessus infection leads to enhanced production of type 1 interferon and NLRP3 inflammasome activation in murine macrophages via mitochondrial oxidative stress.","volume":"16","author":"Kim","year":"2020","journal-title":"PLoS Pathog."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1080\/15548627.2019.1582743","article-title":"SIRT3 promotes antimycobacterial defenses by coordinating mitochondrial and autophagic functions.","volume":"15","author":"Kim","year":"2019","journal-title":"Autophagy"},{"key":"B14","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1007\/s10875-013-9978-y","article-title":"Mycobacterium massiliense induces inflammatory responses in macrophages through Toll-like receptor 2 and c-Jun N-terminal kinase.","volume":"34","author":"Kim","year":"2014","journal-title":"J. Clin. Immunol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1080\/21505594.2020.1809961","article-title":"Sirtuin 3 is essential for host defense against Mycobacterium abscessus infection through regulation of mitochondrial homeostasis.","volume":"11","author":"Kim","year":"2020","journal-title":"Virulence"},{"key":"B16","doi-asserted-by":"publisher","first-page":"648","DOI":"10.3390\/cells9030648","article-title":"The peroxisome proliferator-activated receptor alpha- agonist gemfibrozil promotes defense against Mycobacterium abscessus infections.","volume":"9","author":"Kim","year":"2020","journal-title":"Cells"},{"key":"B17","doi-asserted-by":"publisher","first-page":"3283","DOI":"10.4049\/jimmunol.1601920","article-title":"PPAR-alpha activation mediates innate host defense through induction of TFEB and lipid catabolism.","volume":"198","author":"Kim","year":"2017","journal-title":"J. Immunol."},{"key":"B18","doi-asserted-by":"crossref","first-page":"3908061","DOI":"10.1155\/2017\/3908061","article-title":"The role of IL-17 and related cytokines in inflammatory autoimmune diseases.","volume":"2017","author":"Kuwabara","year":"2017","journal-title":"Mediators. Inflamm."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2179","DOI":"10.3389\/fmicb.2018.02179","article-title":"The role of antibiotic-target-modifying and antibiotic-modifying enzymes in Mycobacterium abscessus drug resistance.","volume":"9","author":"Luthra","year":"2018","journal-title":"Front. Microbiol."},{"key":"B20","first-page":"191","article-title":"Respiratory infections due to nontuberculous mycobacterias.","volume":"150","author":"Maiz Carro","year":"2018","journal-title":"Med. Clin."},{"key":"B21","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1111\/mmi.12387","article-title":"Identification and characterization of the genetic changes responsible for the characteristic smooth-to-rough morphotype alterations of clinically persistent Mycobacterium abscessus.","volume":"90","author":"Pawlik","year":"2013","journal-title":"Mol. Microbiol."},{"key":"B22","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/5584_2016_45","article-title":"Non-tuberculous mycobacteria: classification, diagnostics, and therapy.","volume":"944","author":"Porvaznik","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"B23","doi-asserted-by":"crossref","first-page":"573844","DOI":"10.3389\/fmicb.2020.573844","article-title":"Salmonella and S. aureus escape from the clearance of macrophages via controlling TFEB.","volume":"11","author":"Rao","year":"2020","journal-title":"Front. Microbiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1997","DOI":"10.4049\/jimmunol.0802181","article-title":"Mycobacterium abscessus glycopeptidolipids mask underlying cell wall phosphatidyl-myo-inositol mannosides blocking induction of human macrophage TNF-alpha by preventing interaction with TLR2.","volume":"183","author":"Rhoades","year":"2009","journal-title":"J. Immunol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"3040","DOI":"10.1128\/iai.70.6.3040-3052.2002","article-title":"Differential regulation of the mitogen-activated protein kinases by pathogenic and nonpathogenic mycobacteria.","volume":"70","author":"Roach","year":"2002","journal-title":"Infect. Immun."},{"key":"B26","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1111\/j.1462-5822.2010.01565.x","article-title":"Overexpression of proinflammatory TLR-2-signalling lipoproteins in hypervirulent mycobacterial variants.","volume":"13","author":"Roux","year":"2011","journal-title":"Cell. Microbiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"160185","DOI":"10.1098\/rsob.160185","article-title":"The distinct fate of smooth and rough Mycobacterium abscessus variants inside macrophages.","volume":"6","author":"Roux","year":"2016","journal-title":"Open Biol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1165\/rcmb.2007-0413oc","article-title":"Mycobacterium abscessus and M. avium trigger toll-like receptor 2 and distinct cytokine response in human cells.","volume":"39","author":"Sampaio","year":"2008","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1046\/j.1462-5822.2003.00263.x","article-title":"Macrophage signalling upon mycobacterial infection: the MAP kinases lead the way.","volume":"5","author":"Schorey","year":"2003","journal-title":"Cell. Microbiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"6202","DOI":"10.3390\/ijms21176202","article-title":"MmpL3 inhibition: a new approach to treat nontuberculous mycobacterial infections.","volume":"21","author":"Sethiya","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"343","DOI":"10.3201\/eid170310060","article-title":"Nontuberculous mycobacteria in respiratory tract infections, eastern Asia.","volume":"17","author":"Simons","year":"2011","journal-title":"Emerg. Infect. Dis."},{"key":"B32","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1055\/s-0038-1651494","article-title":"Treatment of Mycobacterium abscessus complex.","volume":"39","author":"Strnad","year":"2018","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2541","DOI":"10.3390\/jcm9082541","article-title":"General overview of nontuberculous mycobacteria opportunistic pathogens: Mycobacterium avium and Mycobacterium abscessus.","volume":"9","author":"To","year":"2020","journal-title":"J. Clin. Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1159\/000445906","article-title":"Pulmonary disease caused by non-tuberculous mycobacteria.","volume":"91","author":"Wassilew","year":"2016","journal-title":"Respiration"},{"key":"B35","doi-asserted-by":"crossref","first-page":"352371","DOI":"10.1155\/2014\/352371","article-title":"Functional roles of p38 mitogen-activated protein kinase in macrophage-mediated inflammatory responses.","volume":"2014","author":"Yang","year":"2014","journal-title":"Mediators Inflamm."},{"key":"B36","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1021\/acs.jnatprod.9b01095","article-title":"Antimycobacterial rufomycin analogues from Streptomyces atratus strain MJM3502.","volume":"83","author":"Zhou","year":"2020","journal-title":"J. Nat. Prod."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.695024\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T03:30:05Z","timestamp":1628566205000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.695024\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,10]]},"references-count":36,"alternative-id":["10.3389\/fmicb.2021.695024"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2021.695024","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,10]]},"article-number":"695024"}}